There are classic psychedelics (psilocybin, LSD, DMT) and non-classic psychedelics (ketamine, MDMA) that receive a lot of scientific and public attention regarding their potential mental health benefits. These are substances that, when combined with psychotherapy, can be helpful in resolving or alleviating conditions such as depressive and anxiety disorders, post-traumatic stress disorder (PTSD), and addiction. There are also other non-classic psychedelics that are receiving increased attention for their ability to effectively improve people’s mental health, including 5-MeO-DMT and ibogaine.
In spite of the ‘psychedelic renaissance’ (the past decade or so of burgeoning research into these compounds and their benefits), one classic psychedelic has been left behind: mescaline. This compound – found naturally in cacti such as peyote (Lophophora williamsii), San Pedro (Echinopsis pachanoi), and Peruvian Torch (Echinopsis peruviana) – receives hardly any attention in comparison to the other psychedelics mentioned. This is despite the fact that a mescaline experience can be just as powerful and transformative as an experience with any other psychedelic.
What can explain this dearth of interest? Why are there no calls for mescaline-assisted psychotherapy? I want to highlight some of the possible reasons why and argue that this overlooking of mescaline is a mistake. This neglected compound is a promising tool for psychotherapy, one that many people would find preferable to other psychedelics.
The Therapeutic Potential of Mescaline
Mescaline is the psychedelic for which we have the earliest evidence of human use. Dried peyote buttons, around 5,700 years old, have been discovered in a cave on the Rio Grande in Texas, while at Chavin de Huantar, a temple complex in the Peruvian Andes thought to date as early as 1,200 BC, you can find a stone carving showing a part-human, part-jaguar figure clutching a San Pedro cactus.
Currently, the Tarahumara, Tepehúan, and Huichol peoples of northern Mexico, as well as the Navajo and Comanche in the southern United States, use peyote in a ritualistic setting for the purposes of healing and making contact with the spirit world. In addition, members of the Native American Church (NAC) – a Pan-Indian religion made up of different Native American tribes – participate in all-night peyote ceremonies as a way to receive visions and messages from the Great Spirit (a supreme being).
In high enough doses, mescaline can indeed induce profound visions, healing, and wisdom, much like ayahuasca and psilocybin mushrooms. Interestingly, however, the writer Mike Jay claims that for indigenous peoples using mescaline-containing cacti, not much attention is paid to the visions that arise; the focus is instead on the insights received. This contrasts with early Western experimenters, who focused a great deal on the visual aspect of the mescaline experience. These literary, scientific, and philosophical figures included Havelock Ellis, J.A. Symons, Jean-Paul Sartre, Aldous Huxley, and H.H. Price.
The most well-known account of the mescaline experience is Huxley’s The Doors of Perception (1954), from which we can see that the compound is capable of inducing profound experiences and philosophical insights. Moreover, when the British MP Christopher Mayhew took mescaline live on a BBC Panorama show in 1955, we saw how mescaline can cause mystical effects: after the experience, Mayhew said “on many occasions that afternoon I existed outside time”; it was an experience that took him “beyond absolute time”.
While many people find that mescaline does not induce mystical effects as easily as other psychedelics, it still certainly can include effects like ego dissolution, insightfulness, a sense of the ‘divine’, feelings of unity, transcendence of time and space, ineffability, and deeply felt peace and joy. But why is this relevant in the context of psychotherapy? Well, psychedelic researchers maintain that the mystical experience drives the efficacy of psychedelic-assisted therapy. Indeed, patients with depression who show the greatest improvements in their symptoms following psilocybin therapy are those who score high on questionnaires measuring mystical-type experiences.
Since mescaline can lead to these experiences, then there is every reason to think it can also be helpful in the treatment of depression, for instance. But mystical effects are not the only aspect of psychedelics that have therapeutic value. These compounds also help benefit people’s mental health by:
- Increasing connection to one’s emotions
- Producing emotional breakthroughs
- Enhancing spirituality and emotional regulation
- Encouraging acceptance of distressing emotions
- Eliciting insights
- Increasing psychological flexibility
- Altering one’s sense of self
These are all effects that mescaline is capable of causing, which users of the compound often report.
Besides indirectly connecting mescaline use with improved mental health (based on studies with other psychedelics), as well as anecdotal reports of its benefits, there is some (limited) research on the therapeutic potential of mescaline.
A 2015 study, published in the Journal of Psychopharmacology, showed that lifetime use of classic psychedelics, including mescaline, was associated with reduced psychological distress and suicidality (suicidal thinking, planning, and attempts). The authors conclude: “These findings indicate that classic psychedelics may hold promise in the prevention of suicide”.
A 2021 study, published in the journal ACS Pharmacology & Translational Science, found that the use of mescaline appears to be associated with improvements in mental health conditions. Researchers recruited 452 adults from around the world who had used mescaline at least once. Participants then completed a wide-ranging questionnaire about their experience, well as a mental health assessment looking at symptoms of depression, anxiety, PTSD, alcohol misuse or alcohol use disorder, and drug misuse or drug use disorder.
Around one-third of participants said their mescaline experience was among the top five most personally meaningful or spiritually significant experiences of their lives. Nearly half indicated they experienced depression or anxiety at the time of their mescaline use, and among those who had depression, 86% reported improvements in the condition after using the drug, while among those who had anxiety, 80% reported improvements. However, most participants did not take mescaline with the intention of bettering their mental health.
The researchers found that mental health benefits were associated with specific aspects of the psychedelic experience, including more mystical-type effects, greater psychological insight, and more ego dissolution effects. The authors, nonetheless, add some caveats:
It is important to note the methodological limitations of our study and to urge caution when interpreting these findings. As this was a cross-sectional study, we cannot infer causality regarding the impact of mescaline on psychiatric conditions. Results are also limited by possible self-selection by individuals favorably disposed toward psychedelic experiences.
Nevertheless, the results from our study indicate that when administered in a naturalistic setting, mescaline may facilitate unintended improvements in self-reported depression, anxiety, PTSD, and substance use disorders.
Research from 1974 suggests that peyote could be useful in the treatment of alcoholism among Native Americans. Also, a 2005 study published in Biological Psychiatry found no evidence of long-term psychological or cognitive deficits among Native Americans who use peyote regularly in a religious context. The researchers who published the 2021 study on mescaline published a later 2022 paper, in the Journal of Psychopharmacology, noting that the substance has a “low potential for abuse”. However, they found that survey participants, overall, “rated the acute mystical-type effects as “moderate,” ego-dissolution and psychological insight effects as “slight,” and challenging effects as “very slight.”” This rating of challenging effects is encouraging, but if mescaline does not produce mystical-type, ego dissolution, and psychological insight effects as strongly or reliably as psilocybin, ayahuasca, or LSD, then its therapeutic potential may be relatively lower.
But research on mescaline is lacking. Controlled, clinical trials are needed to establish just how effective mescaline is for treating mental health conditions. Survey studies, after all, are subject to issues like selection bias (those who have benefited from mescaline may be more likely to fill out questionnaires related to its use compared to those who have been negatively impacted by it).
The Unique Benefits of Mescaline
Mescaline should not be neglected as a tool for psychotherapy as it seems to have some unique benefits. Most likely due to being a phenethylamine (as MDMA and 2CB also are), the mescaline headspace tends to be more lucid, more euphoric, and easier to control than psilocybin, for example. Many actually compare mescaline to being like MDMA combined with LSD or psilocybin. The mescaline experience is often characterised by feelings of empathy, connection, love, and physical euphoria. While it is, of course, possible to have a challenging and distressing experience when taking mescaline, it seems to be less likely to occur than with LSD or psilocybin.
The clearer, easier-to-navigate headspace of a mescaline experience is useful in a clinical setting, as this may reduce the risks of adverse psychological reactions. The 2022 study published in the Journal of Psychopharmacology indicates this is the case – alongside the “very slight” challenging effects of mescaline, only 1% of survey respondents reported psychological problems related to the use of mescaline and none reported seeking any medical attention. Many people who struggle with a mental health condition – especially one that is severe, chronic, and unresponsive to other treatments – could be eager to try psychedelic-assisted therapy as an alternative, effective option. Yet they may be hesitant and worried about experiencing states of anxiety, fear, panic, loss of control, confusion, and feeling overwhelmed. If mescaline is used, such reactions might be less likely to occur.
It should be underscored that the common anxiety seen in clinical trials with psilocybin is transient, so it doesn’t last long. Nonetheless, these trials involve small numbers of people. When psychedelic therapy becomes available to the masses, it is possible that more serious adverse reactions will occur. Indeed, it is not uncommon for people to experience strong negative experiences following the ingestion of psilocybin mushrooms, even in supportive settings. If research could show that mescaline leads to fewer negative subjective effects than other psychedelics, then this would make it a promising adjunct to psychotherapy.
Some Reasons Why Mescaline Has Been Neglected in Research
Mescaline was first synthesised in the laboratory in 1919, and then from 1920, mescaline sulphate was available as a pure drug from European pharmacy suppliers such as Merck. Psychologists and neurologists, particularly in Germany, gave mescaline to dozens of subjects, generating hundreds of pages of reports documenting their visions and revelations. By the 1950s, when psychiatry embraced the biomedical approach, mescaline was widely used in schizophrenia research.
LSD already existed by this time (the Swiss chemist Albert Hofmann synthesised it in 1943). Eventually, psychiatrists and pharmacologists agreed that mescaline and LSD intoxication were very similar. However, Jay notes:
The most significant difference was the dose. LSD was massively more potent: a gram of mescaline was around three doses, but a gram of LSD was thousands. This made LSD more intriguing to the mind scientists, since it was obviously working with far greater precision on whatever brain mechanisms these drugs were activating. It was also, of course, much more economical.
So, we begin with the fact that mescaline is more expensive to produce. Doses of pure, synthetic psilocybin are likewise much lower than those of mescaline (25 mg and 400 mg, respectively, for a strong experience). The typical doses of mescaline also explain why clandestine chemists don’t bother to make it, as it’s not as profitable as producing psychedelics such as LSD or 2CB. Synthetic mescaline is, therefore, very rare to find, although some vendors have been known to sell it on the dark web.
Researchers may also overlook mescaline in favour of other psychedelics because of its long duration (which would also make mescaline-assisted psychotherapy more expensive than the psilocybin variety, due to the greater amount of time involved). It is not unheard of for a high-dose mescaline trip to last 16+ hours. In comparison, a psilocybin experience lasts around six hours, while an LSD experience tends to last 12 hours (sometimes longer).
Having said that, the subjective effects of mescaline can last around the same amount of time as those of LSD for many people. Furthermore, ibogaine-assisted therapy is being researched, with treatment centres operating in several countries, and these involve journeys lasting 24 hours or longer.
Another possible reason why there is less of a push for mescaline-assisted psychotherapy could be due to nausea. Mescaline is known to lead to more nausea and vomiting than psilocybin. Even in its synthetic form, this compound can be hard on the stomach, especially in high doses (which would be used in psychedelic therapy).
Researchers from one of the 2021 mescaline studies, nonetheless, state that nausea and vomiting are more frequently linked to consuming peyote than other methods of mescaline ingestion. It has been suggested that this is due to its bitter taste, as well as other chemicals found in the plant, rather than just mescaline. It should be emphasised, however, that San Pedro can still produce noticeable and prolonged nausea.
When it comes to synthetic mescaline, volunteers in a 1992 study who took this form of the drug did not report nausea or vomiting. This doesn’t mean the pure, synthetic version won’t induce such effects, of course, as many people (including Jay) have experienced nausea from it. The overall likelihood, though, is that such physical effects will be less likely or not as intense compared to consuming peyote or San Pedro. For example, James, who was eager to have a mystical experience from peyote, instead had a day of vomiting and diarrhoea.
Despite the potential for mescaline to have more (initially) unpleasant physical effects than psilocybin or LSD, many people are willing to accept this price for the rewards of the experience. Patients wanting to sign up for psychedelic-assisted psychotherapy should likewise have this option.
Some researchers and psychedelic companies are now starting to show interest in the therapeutic potential of mescaline. MindMed, for instance, has gained approval for a placebo-controlled trial – led by pharmacologist Matthias Liechti at the University Hospital in Basel, Switzerland – that will evaluate the acute effects of different doses of mescaline and the role of the serotonin 5-HT2A receptor in mescaline-induced altered states. This kind of data is currently lacking in the existing literature. Dr. Miri Halperin Wernli, President of MindMed, has stated:
We believe the drug will have a powerful effect on enhancing the communication between different parts of the brain in unique ways that are otherwise inaccessible to the conscious mind. As we move forward, further studies on patient populations will be targeted to help us distinguish the relationship between the drug-induced experience and its integration into the psychotherapeutic process. The hope is that this will then allow a better understanding of the behavioral changes and the unique effect of these powerful drugs on neuroplasticity.
Another approved, placebo-controlled study, also led by Liechti, will compare the acute effects of LSD, psilocybin, and mescaline. Its main objective is to “determine whether LSD, psilocybin and mescaline produce qualitatively similar subjective alterations of mind and associated brain activity patterns despite their unique receptor activation profiles.”
XPhyto Therapeutics, a bioscience company based in Vancouver, Canada, believes mescaline displays particular promise for the treatment of addiction and a broad range of mental health conditions. And for this reason, the company plans to develop industrial-scale pharmaceutical-grade production processes for the wholesale market. “We see a significant market opportunity in the production of pharmaceutical mescaline and the standardisation of dosage formulations with precise, predictable and efficient drug delivery for clinical study and therapeutic use,” says XPhyto Chief Executive Officer Hugh Rogers. The company’s mescaline formulation will aim to minimise nausea and offer patients more predictable onset times.
In addition, the company Journey Colab is developing synthetically-derived psychedelics to be used as a treatment for addiction, starting with their patent-protected synthetic mescaline HCl (JOUR-5700) for the treatment of alcohol use disorder (AUD). This widespread social ill is a chronic, relapsing condition, and the Centers for Disease Control and Prevention (CDC) states that excessive alcohol use in the US claims more than 140,000 lives every year.
The hope is that the company’s clinical trials will demonstrate that mescaline-assisted therapy can help people struggling with AUD achieve durable remission, gaining FDA approval for the treatment in the process. Its first clinical study will be a Phase 1 trial, focused on safety, which will be followed by additional clinical trials investigating effectiveness and safety in larger numbers of patients. Once (or if) these aims are achieved, mescaline could – as with psilocybin – prove to be an effective psychedelic in treating alcoholism, although it is unclear which one will prove to be the more efficacious compound.
Jeeshan Chowdhury, the founder and chief executive of Journey Colab, told Lucid News: “Mescaline’s unique properties — that it is long-acting and less potent — make it more tolerable. These are features. They are not bugs.” However, the higher costs associated with therapists committing to the time needed for mescaline sessions – as well as the competition from psilocybin – meant that one venture capitalist decided not to invest in the company. Several biotech companies are developing analogues of mescaline (of which many already exist), in the hope of reducing the duration of the experience and lessening nausea, which may make the use of these compounds a more attractive treatment option, although safety and efficacy still need to be determined. There is also the question of whether the power of peyote can translate into western medicine, given that the group setting – the collective experience – may contribute to the therapeutic effects (although this applies to psychedelics, in general).
Moreover, some people may be convinced that to maximise the true potential of mescaline, you need to take it in its cactus form, as it is believed that the other alkaloids modulate and enhance the overall quality of the experience. (Peyote contains more than 50 psychoactive alkaloids, and San Pedro contains many besides mescaline as well.)
In a piece for Chacruna, Benjamin Bury argues that we should opt for synthetic mescaline in light of declining peyote populations, a trend which is especially concerning for those indigenous communities that traditionally use the latter. (Using San Pedro cactus, which grows much quicker than peyote and is not under threat, would be another sensible and ethical alternative). At the end of his article, Bury observes how the psychedelic renaissance has been particularly marked by the recognition of the healing potential of plant medicines. Relating this to synthetic mescaline, he writes:
Given this emphasis, I would like to address a potential assumption that may have arisen implicitly throughout existing cultural presuppositions regarding bioactive compounds and the public discourse surrounding this movement: that synthetic psychedelics do not possess the same depth or capacity for personal insight and healing. The psychedelic experience arises as a result of the meeting of mind, substance, and situation. While that might sound trite, it makes the case that, ultimately, set and setting are most important for determining the trajectory and transformative power of an experience. The substance consumed is but one part of the setting. Although not a direct equivalent to a peyote experience, synthetic mescaline is of potentially equal value and can certainly catalyze deeply profound and meaningful experiences for those who approach its use with the appropriate intentions and respect for the experience.
People may think that pure, synthetic psychedelics take the ‘magic’ or ‘spiritual depth’ out of the plant or mushroom it’s found in, but this isn’t the case. Many people have life-changing and highly meaningful experiences with synthetic mescaline (Huxley and Mayhew’s trips are cases in point). The same applies to the synthetic psilocybin used in clinical trials. It’s important to keep this in mind when considering mescaline-assisted psychotherapy, as it is the synthetic version of the drug that would be used in a clinical setting. (Side note: due to the influence of one’s mindset before going into a psychedelic experience, it is possible that believing the cactus experience to be deeper than the synthetic one could encourage these differences in effects to occur.)
Based on the above discussion, I see no reason why combining mescaline with psychotherapy should not be an option for patients, especially since many will be comfortable with a longer trip and more attracted to the mescaline headspace. This compound has been undeservedly neglected in conversations about psychedelic-assisted therapy, but with new studies on the horizon, this situation could soon change.
This article originally appeared on the Chemical Collective blog